1. Field of the Invention
The present invention relates to compositions and methods used for healing of wounds and proliferating cells in culture.
2. Description of the Background Art
There is continuing medical interest in materials and methods which promote and accelerate the healing of wounds. Wound-healing strength can be measured in newtons (N) or expressed in g/mm.sup.2 (.times.1000/9.8) (Tensometer 10, Monsanto Co., St. Louis, Mo., U.S.A.) utilizing a linear skin incision model in rats, as is well documented (Ross, "The Fibroblast and wound repair", Biological Review 43: 51-96 (1968); Peacock, Jr., "Wound Repair", Ed. 3, W. B. Saunders, Philadelphia (1984); Mustoe et al., "Accelerated healing of incisional wounds in rats induced by transforming growth factor-.beta.", Science 237: 1333-1335 (1987)). This is a recognized model in assessing a generation of wound strength, the most important aspect of wound-healing (Mustoe et al., supra).
As described in U.S. Pat. No. 5,156,847, issued Oct. 20, 1991 to Lewis et al., U.S. Pat. No. 5,474,782, issued Dec. 12, 1995 to Winter et al., and in Porras-Reyes et al., Proc. Soc. Exp. Bio. Med. 203: 18-25 (1993), wound-healing compositions of the alkaloid taspine, dissolved in a non-aqueous solvent, such as dimethyl sulfoxide (DMSO) were shown to promote wound healing. However, taspine is practically insoluble in most conventional vehicles, including water, alcohol, saline solutions, and the like. Thus, there remains in the art a need for new compositions and methods which can be effectively, safely, and economically administered and utilized to accelerate the healing rate of wounds, and which preferably are soluble in aqueous media.
Additionally, Lewis et al., Winter et al., and Porras-Reyes et al. show promotion of wound-healing solely by measuring tensile strength using a linear skin incision rat method. Accordingly, there is a need in the art for new methods in addition to the linear skin incision model in rats which allow direct observations and measurements of wound-healing acceleration in taspine and taspinates and their aporphine-derived analogs and other aporphine-derived compounds. Also, there is a need in the art to provide new methods showing fibroblast and other types of cellular proliferation necessary to accelerate wound repair and appropriate modeling.